Modeling of electron induced damage in biological tissue

In the project Modeling of electron-induced damage in biological tissue we investigate the role of low energy electrons interacting with biological systems by means of simulations. Experiments have revealed that low energy electrons are produced in our bodies via high energy radiation such as cosmic radiation or during radiation therapy. The results have shown that these electrons can induce damage to the DNA which in some cases might lead to improper reparation and subsequently eventually to mutation of cells or even cell death. These phenomena are utilized in radiotherapy. However, also the healthy tissue surrounding the tumor is effected by the irradiation. Not only DNA can be damaged but also chemotherapeutical drugs which are sometimes used in combination with radiotherapy. The modification of these drugs can either have positive (more efficient destruction of cancer cells) or negative (damage of healthy tissue) effects. For a better understanding and targeted administration of chemotherapeutical drugs, the principle mechanisms inside the cell need to be understood. On the basis of very accurate quantum chemical methods, a database should be established which will allow to describe reliably DNA fragments in their natural surroundings, i.e. solvated in water together with other biomolecules and radicals. These very accurate methods can only be used for very small systems. Combined with less accurate but fast methods, a computational protocol shall be constructed to describe and understand large systems and their behavior in the presence of low energy electrons. On a time scale beyond this project, the results are expected to lead towards intelligent, target-oriented drug design and coordinated radio-chemotherapeutical cancer treatment.

In the project 'Modeling of electron-induced damage in biological tissue' the basis for a multi-scale approach to quantitatively describe the effects of low-energy electrons on substances used in clinical radio-chemotherapy embedded in biomolecular environments could be established. Experiments have shown that low-energy electrons are generated in our bodies by high-energy radiation such as cosmic rays or during radiotherapy. The results have shown that these electrons can cause damage to the DNA, which in some cases can lead to faulty repair and subsequently mutation of cells or even cell death. These phenomena are exploited in radiotherapy. But the healthy tissue surrounding the tumour is also affected by the radiation. Not only the DNA can be damaged, but also chemotherapeutic drugs, which are sometimes used in combination with radiotherapy. The change in these drugs can have either a positive effect (more efficient destruction of cancer cells) or a negative effect (damage to healthy tissue). For a better understanding and targeted delivery of chemotherapeutic drugs, the basic mechanisms within the cell need to be understood. To provide the basis for this goal, this project analysed and evaluated the accuracy of the results of quantum chemical calculations. Diagnostics were developed to estimate the precision of the simulations. Furthermore, the interaction of electrons with different radiosensitizers such as cisplatin but also with DNA sequences was investigated. These results showed the influence of the biomolecular environment such as ions or aqueous solution on molecular processes.